STEROID HORMONES, HIV-INFECTED CELLS AND HIV GENES

类固醇激素、HIV 感染细胞和 HIV 基因

• 批准号: 3241641
• 负责人: E B THOMPSON
• 金额: $ 15.11万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-02-01 至 1994-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3241641
• 关键词: AIDS; CD4 molecule; HIV infections; Herpesviridae disease; cell bank /registry; clone cells; cytolysis; estrogens; gene expression; glucocorticoids; hormone receptor; human immunodeficiency virus; human tissue; messenger RNA; molecular pathology; mouse mammary tumor virus; nuclear magnetic resonance spectroscopy; peptide hormone biosynthesis; progestins; ribosomal RNA; steroid hormone; transfection; transposon /insertion element; virus cytopathogenic effect; virus genetics

This project is designed to do two things: first, to test the hypothesis that changes in steroid hormone effects are involved in the direct and indirect cytopathicity of HIV; and second, to use a DNA response element for glucocorticoids as a cis-active control over HIV genes to determine their functions quantitatively. Steroid hormones have profound effects on lymphoid cells directly and also indirectly, through influences on many peptide hormones and their receptors. We will investigate the effects of steroids on peripheral blood lymphoid cells of HIV infected individuals and on several infected cell lines. This will require studies of cellular effects of steroids, analysis of steroid receptors, and examination of the interactive effects of steroids with several peptide hormones and their receptors. Limited reports raise the possibility that HIV is glucocorticoid-inducible. We will thoroughly test this possibility. The exact function of several HIV genes is unknown, as are the quantitative relationships between specific gene products and overall HIV replication and cytopathicity. We will place the glucocorticoid response element from the MMTV LTR in a cis relationship to HIV or specific HIV genes, to provide glucocorticoid-regulatable HIV genes for study in transfected cells. Our clonal lines of CEM cells with known lesions in the glucocorticoid response system, should be of particular value in these studies.

这个项目旨在做两件事：第一，测试 假设类固醇激素效应的变化涉及 艾滋病毒的直接和间接细胞病变;第二，使用 作为顺式活性对照的糖皮质激素的DNA反应元件 来定量地确定它们的功能。 类固醇激素直接对淋巴细胞有深远的影响 也间接地通过影响许多肽类激素 和它们的受体。 我们将研究类固醇的作用 对HIV感染个体的外周血淋巴样细胞的作用， 感染的细胞系上。 这将需要研究 类固醇的细胞效应，类固醇受体的分析， 检查类固醇与几种药物的相互作用 肽激素及其受体。 有限的报告提出， 艾滋病病毒是糖皮质激素诱导的可能性。 我们将 彻底检验这种可能性。 艾滋病毒的几个基因的确切功能尚不清楚， 特定基因产物之间的定量关系 总体HIV复制和细胞病变。 我们将放置 糖皮质激素反应元件从MMTV LTR在一个顺式 与HIV或特定HIV基因的关系，以提供 糖皮质激素可调节的HIV基因，用于转染的 细胞 我们的CEM细胞的克隆系与已知的病变， 糖皮质激素反应系统，应该是特别的价值， 这些研究。